FR2859603A1 - USE OF NEOHESPERIDINE DIHYDROCHALCONE IN ORAL COMPOSITIONS COMPRISING VITAMINS AND / OR MINERALS - Google Patents

Abstract

Use of NHDC alone to protect vitamins against degradation, preferably in chewable compounds.Use of NHDC in combination with sorbitol to mask the unpleasant taste of vitamins and / or minerals.

Description

Vitamins and minerals play a major role in all

mechanisms

  physiological aspects of the human body. A diversified diet and, in particular, rich in raw fruits and vegetables should provide the body with all the necessary vitamins and minerals and in sufficient quantities. Nevertheless, dietary habits in industrialized countries are increasingly leading consumers to reduce the consumption of fruits and vegetables in favor of processed fruits and vegetables, which results in the appearance of deficiencies or sub-stresses. vitamins and minerals. All recent epidemiological studies confirm these states of subcarence.

  This situation has led nutritionists to define optimal doses of vitamins and minerals to be consumed each day (recommended dietary intakes or recommended daily intake) and, consequently, to recommend a higher consumption of fruits and vegetables but also a vitamin supplementation. and most often in deficit minerals, in the form of vitamin and mineral fortified foods and dietary supplements.

  Among these many products, the majority combines antioxidant vitamins whose 3 major are: vitamin A (retinol or carotenoids), vitamin E and vitamin C. Indeed, these antioxidant vitamins have the ability to control the production of vitamins. free radicals resulting from the metabolism of oxygen, and whose overproduction is responsible for a very large number of disorders, especially at the cardiovascular level, immunity, cancer, cutaneous, accelerated aging, neuro-degenerative diseases, etc. These vitamins can be formulated in various forms, mainly as tablets, capsules, soft capsules or syrups.

  For reasons of cost and ease of setting, the 2 most used forms are tablets (chewable or swallow) and capsules.

  Antioxidant vitamins in the form of tablets and capsules always have a problem: stability over time. Indeed, their physiological antioxidant activity is linked to a very high affinity for oxygen in the air. Since it is technically and economically difficult to condition these forms so that they are not in contact with air and oxygen, there is always a certain degradation of these vitamins, which forces not only to over titrate them to the manufacturing, but also to limit the expiry of the corresponding products.

  It is well known that vitamins, in particular carotenoids, degrade quite rapidly in galenic forms.

  Although the compressed form generally allows an acceptable conservation of carotenoids over several years, on the other hand, it is regularly observed that about 10 to 15% of the carotenoids are degraded in the first months following the manufacture of these tablets.

  In order to limit this problem, until now there have been more or less satisfactory technical solutions, in particular the addition of chemical substances having only an anti-oxidant activity in the galenic form.

  But the effectiveness of these substances is sometimes limited. In addition, these substances having only one function in the formulation their presence increases accordingly the amount of substance to be introduced into the formulation, thereby reducing the amount of active substances present. In addition, these substances are rarely of natural origin, which is contrary to the current demand to use as many ingredients of natural origin as possible.

  It has been discovered, quite fortuitously, that the use of a particular sweetener (ingredient bringing a sweet taste to the formula) in a tablet formula containing these vitamins, protected these vitamins against their degradation, and in particular against their oxidation.

  This sweetener is Neohesperidin DiHydroChalcone (NHDC) obtained by hydrogenation of a natural flavonoid extracted from citrus fruit and, in particular, grapefruit.

  It is an internationally approved ingredient, referenced in Europe under the code 5 E 959 and recognized GRAS (Generally Recognized As Safe) in the USA.

  This effect was quite unexpected, since this sweetener had been introduced into this tablet formula only for organoleptic purposes, to bring a sweet taste to the formulation.

  It is known in patent FR 2 113 678 that NHDC can be used to preserve and prolong the quality of the perfume in chewing gums or confectionery products containing essential oils containing flavoring substances. However, the mechanism of action underlying this use has not been elucidated by the author of this patent.

  In addition, vitamins and especially carotenoids differ from perfumes whose NHDC prolongs the duration, in terms of their chemical structure. Indeed the many lipophilic ingredients of an essential oil have nothing to do with the chemical structure of vitamins, vitamins can be hydrophilic or lipophilic.

  Dietary supplements containing vitamins and minerals in the form of capsules, soft capsules or tablets are intended to be swallowed: these forms must therefore be of relatively modest size; therefore, each unit contains between 200 and 400 mg of powder.

  When the quantities of vitamins and minerals to be supplemented are quite important, these galenic forms are poorly adapted because, to allow a sufficient intake, it would be necessary to swallow at least 8 to 12 units per day, which is restrictive and does not contribute to a consumption. regular doses needed.

  It is therefore particularly interesting to use another dosage form: the chewable tablet. This form is not intended to be swallowed, it can be much larger size, up to 4 to 5 grams, allowing the intake of much higher amounts of vitamins and minerals in one take.

  This form therefore has a real advantage over the forms to be swallowed but involves another constraint, the taste, since the active substances come into direct contact with the taste receptors of the oral cavity, which is not the case with other forms.

  Therefore the major constraint of these chewable tablets is to present an acceptable taste and even, if possible, pleasant. However, a number of vitamins have a rather unpleasant taste, including carotenoids (beta-carotene, lycopene, etc.), vitamin C and most of the vitamins of group B. It is the same for certain minerals, including iron and zinc.

  To solve these taste problems of chewable tablets containing vitamins and minerals, galenists have several technological means: - coating substances with a bad taste by neutral ingredients allowing a masking of taste. This technology has the disadvantage of increasing the amount of substance to be introduced into the tablet and significantly increasing the cost of these products. In addition, during chewing, this coating is often partially destroyed, thereby reducing the effect of taste masking.

  - use of flavors and / or sweeteners to mask the taste of vitamins and minerals.

  The sweeteners can be sugars (sucrose, fructose, glucose, mannitol, sorbitol) but also other substances having a sweetening power (sweetness) more or less intense. Among these sweetening substances other than sugars, it is possible to use substances of natural origin (thaumatin, NHDC) or synthetic substances (acesulfame potassium, sodium saccharin, sodium cyclamate).

  The main difficulty during the formulation of a chewable tablet is to identify the minimum dose of sweetener for effective taste masking.

  Indeed, sugars constituting a relatively large intake of calories (4 kcal / g) and all having a cariogenic power, it is desirable to reduce the intake. In addition, sucrose, although having a high sweetening power, has a glycemic index (ability to raise blood glucose after ingestion) particularly troublesome in diabetic subjects, but also in all people wishing to control their weight.

  Sorbitol, has a sweetening power of about 60% compared to sucrose and a low glycemic index, interesting for the categories of people defined above. However, sorbitol alone does not mask the unpleasant taste of the active ingredients, especially carotenoids.

  On the other hand, the quantities of sweeteners of natural origin or of synthesis are limited by the food regulations in force.

  Thus the NHDC requires, when used alone to mask the taste of the active ingredients such as carotenoids, too large doses, doses at which a bitterness of this sweetener appears. In addition, the European regulation sets a limit dose of use of this sweetener which is 400 mg / kg for food supplements containing vitamins and / or minerals in the form of syrup or chew, which is not always sufficient to obtain an optimal masking of the taste of the assets.

  Tests for possible synergy of the sweetening powers of several sweeteners have been carried out (Schiffman et al., Brain Research Bulletin, Vol. 38, No. 2, pp.105-120, 1995). However, although calculation method 1 seems to show a synergy between NHDC and sorbitol, this synergy appears only at a low dose (corresponding to a solution comprising 3% sucrose) and not at higher doses, in particular corresponding to 1 290 mg of sorbitol per 0.9 mg of NHDC, for which only an additivity between the sweetening powers is observed.

  In addition, calculation method 2 concludes that there is no synergy at the three doses tested.

  In addition, this study was carried out on aqueous compositions comprising only the two sweeteners. Thus, the masking power of these sweeteners has not been tested, particularly with regard to the taste of carotenoids in chewable tablets.

  Surprisingly, it has been discovered by the inventors of the present application that the combination of sorbitol and NHDC in chewable tablets makes it possible to mask the taste of the active ingredients, such as carotenoids, and that there is a synergy. between these two sweeteners in this use.

  The present invention thus relates to the use of NHDC to protect vitamins against their degradation, in particular against their oxidation.

  Advantageously, the vitamins are chosen from vitamin A, carotenoids, vitamin C, vitamin E, group B vitamins and mixtures thereof.

  In an advantageous embodiment, the vitamin is a carotenoid, advantageously beta-carotene, lycopene and / or vitamin A. In a first embodiment of the invention, the NHDC and the vitamin (s) are found in a composition intended for oral administration, advantageously in the form of chewable tablets, swallowable tablets, capsules, capsules, syrup, powder, granules which are dispersible in water, etc.

  In a second embodiment of the invention, the amount of NHDC in the composition is between 0.01 and 0.1% by weight.

  In another embodiment of the invention, the composition further comprises sorbitol.

  The composition may also include minerals, preferably selected from iron, zinc, selenium and mixtures thereof.

  In a particular embodiment of the invention, the composition is in the form of a chewable tablet comprising 18 to 71% by weight of sorbitol and 0.01 to 0.05% by weight of NHDC, a ratio of NHDC / sorbitol between 0.015% and 0.3%. Advantageously, the chewable tablet comprises 53.6% by weight of sorbitol and 0.03% by weight of NHDC, ie an NHDC / sorbitol ratio of 0.056%.

  In another embodiment of the invention, the composition comprises vitamin A, natural vitamin E, natural vitamin C, natural beta carotene, natural lycopene, zinc oxide and natural selenium. , advantageously in the respective proportions below 0.13% by weight, 0.72% by weight, 17.15% by weight, 0.6% by weight, 0.06% by weight, 0.36% by weight and 4% by weight. 47% by weight.

  The present invention also relates to the use of NHDC in combination with sorbitol to mask the taste of the vitamins and / or minerals of the composition, preferably their bad taste.

  In particular the composition is in the form of a chewable tablet. Advantageously, the vitamins are chosen from vitamin A, carotenoids, vitamin C, vitamin E, group B vitamins and mixtures thereof.

  Advantageously, the minerals are selected from iron, zinc, selenium and mixtures thereof.

  In an advantageous embodiment, the vitamin is a carotenoid, advantageously beta-carotene, lycopene and / or vitamin A. In a particular embodiment of the invention, the composition is in the form of a chewable tablet comprising 18 to 71% by weight of sorbitol and 0.01 to 0.05% by weight of NHDC, an NHDC / sorbitol ratio of between 0.015% and 0.3%. Advantageously, the chewable tablet comprises 53.6% by weight of sorbitol and 0.03% by weight of NHDC, ie an NHDC / sorbitol ratio of 0.056%.

  In another embodiment of the invention, the composition comprises vitamin A, natural vitamin E, natural vitamin C, natural beta carotene, natural lycopene, zinc oxide and natural selenium. , advantageously in the respective proportions below 0.13% by weight, 0.72% by weight, 17.15% by weight, 0.6% by weight, 0.06% by weight, 0.36% by weight and 4% by weight. 47% by weight.

  The present invention finally relates to the use of NHDC in a chewable tablet composition comprising sorbitol, both for protecting the vitamins of the composition, in particular carotenoids, against their degradation, in particular their oxidation, and both, in combination with sorbitol, thanks to a synergistic effect between these two sweeteners, to mask the taste of the vitamins and / or minerals of the composition, advantageously the unpleasant taste of carotenoids.

  The following examples are given as a non-limiting indication.

  Example 1: Use of NHDC to protect vitamins against degradation.

  A food supplement in the form of a chewable tablet of 2800mg (formula in the attached table) is manufactured by direct compression after mixing its ingredients in a powder mixer. 25

  Ingredients Amount put in Equivalence in active formula% pure work Vitamin A 3.53 mg 603 g 0.13 Vitamin E 20.16 mg 10.08 mg 0.72 natural Vitamin C 480.20 mg 120.05 mg 17.15 natural beta-carotene 16.80 mg 1, 68 mg 0.60 natural Natural Lycopene 1.68 mg 84 g 0.06 Zinc Oxide 10.0 08 mg 8.06 mg 0.36 Natural Selenium 125.16 mg 75 g 4.47 sorbitol 1581.30 mg 56.47 Fruit flavor 490 mg 17.50 red 70 mg stearate 2.50 mg NHDC 1.12 mg 0.04 Another tablet is manufactured in which NHDC is replaced by aspartame 5 ( 3.92 mg) and acesulfam (2.8 mg).

  It has been observed, with the formula comprising NHDC, that after one month of storage at room temperature, the contents of beta-carotene and lycopene tablets remained virtually unchanged while in the other formula containing no NHDC, a 3 to 5% drop in content was observed.

  EXAMPLE 2 Synergy Between NHDC and Sorbitol to Hide Bad Taste In order to compare the efficacy between several sweeteners to mask bad taste, a comparative study was carried out.

  Chewable tablets, whose active composition has remained constant (see Table 5 below), have been formulated using sweeteners of various types and amounts.

  Vitamins and Amount Equivalent in Active Mineral Active Ingredients Vitamin A 3.53 mg 603 g Vitamin E 20.16 mg 10.08 mg natural Vitamin C 480.20 mg 120.05 mg natural beta-carotene 16.80 mg 1, 68 mg natural Natural Lycopene 1.68 mg 84 g Zinc Oxide 10 mg 8.06 mg Natural Selenium 125 mg 75 g The first tests to mask the unpleasant taste of the active ingredients were carried out with the reference sugar, ie to say sucrose.

  At the maximum dose of sucrose to make a chewable tablet of acceptable size, that is to say 2,500 mg of sucrose for a 3800 mg tablet, the masking of the taste was not yet satisfactory.

  In fact, the tests have demonstrated that about 3500 to 4000 mg of sucrose are required to have satisfactory masking of the taste, resulting in tablets that are too large.

  Sorbitol has a sweetness of about 60% compared to sucrose. So it is also not enough alone to mask the unpleasant taste of assets.

  NHDC requires too high doses to mask the taste of assets such as carotenoids, a dose at which a bitterness of this sweetener appears. In addition, the European regulation sets a limit dose of use of this sweetener which is 400 mg / kg for food supplements containing vitamins and / or minerals in the form of syrup or chew, which is not enough to get a masking of the taste of the assets.

  By taking a base of 1500 mg of sorbitol per tablet, which corresponds, with the active ingredients to a tablet of approximately 2800 mg having a size perfectly adapted to the use to be chewed, theoretically it was necessary to use a sweetener bringing a sweetening power equivalent to 2600 mg of sucrose (3500 mg 1500 x 0.6).

  Among the tests carried out with different sweeteners, a quite surprising result was observed with the NHDC. Indeed, the sweetening power of this sweetener is about 1500 times that of sugar, it should be used, according to the calculation above, 1.7 mg of NHDC per tablet.

  However, the tablet weighing 2800 mg, the European regulation allows to use only 1.12 mg / tablet, or 34% less than the theoretical dose, which should normally be insufficient to mask the taste of the assets.

  Now, quite unexpectedly, it appeared that this mixture had the best taste among all the tests performed, perfectly masking that of the assets.

This phenomenon can only be explained by a synergy of the masking power between sorbitol and NHDC, thus enabling significantly lower amounts of these two sweeteners to be used.

Claims (10)

  1. Using NHDC to protect vitamins from degradation.   2. Use according to claim 1 characterized in that the vitamins are selected from vitamin A, carotenoids, vitamin C, vitamin E, vitamins of group B and mixtures thereof.   3. Use according to one of the preceding claims, characterized in that the NHDC and the vitamins are in a composition intended for oral administration, advantageously in the form of chewable tablets, tablets to be swallowed, capsules, capsules, syrup, powder, or granules dispersible in water.   4. Use according to one of the preceding claims characterized in that the amount of NHDC in the composition is between 0.01 and 0.1% by weight.   5. Use according to one of the preceding claims characterized in that the vitamin is a carotenoid, preferably beta-carotene, lycopene and / or vitamin A. 6. Use according to one of the preceding claims characterized in that the composition further comprises sorbitol.   7. Use according to one of the preceding claims characterized in that the composition further comprises minerals, preferably selected from iron, zinc, selenium and mixtures thereof.   8. Use according to claim 6 or 7 characterized in that the NHDC in combination with sorbitol is used to mask the taste of the vitamins and / or minerals of the composition, preferably their bad taste.   9. Use according to one of the preceding claims characterized in that the composition is in the form of a chewable tablet comprising 18 to 71% by weight of sorbitol and 0.01 to 0.05% by weight of NHDC.   10. Use according to one of the preceding claims characterized in that the composition comprises vitamin A, natural vitamin E, natural vitamin C, natural beta-carotene, natural lycopene, zinc oxide and natural selenium, preferably in the following respective proportions 0.13% by weight, 0.72% by weight, 17.15% by weight, 0.6% by weight, 0.06% by weight, 0.36% by weight and 4.47% by weight.